title: Suppression of CFTR-mediated Cl secretion of airway epithelium in vitamin C-deficient mice.
abstract: Hyperoxic ventilation induces detrimental effects on the respiratory system, and ambient oxygen may be harmful unless compensated by physiological anti-oxidants, such as vitamin C. Here we investigate the changes in electrolyte transport of airway epithelium in mice exposed to normobaric hyperoxia and in gulonolacton oxidase knock-out (gulo[-/-]) mice without vitamin C (Vit-C) supplementation. Short-circuit current (I(sc)) of tracheal epithelium was measured using Ussing chamber technique. After confirming amiloride-sensitive Na(+) absorption (ΔI(sc,amil)), cAMP-dependent Cl(-) secretion (ΔI(sc,forsk)) was induced by forskolin. To evaluate Ca(2+)-dependent Cl(-) secretion, ATP was applied to the luminal side (ΔI(sc,ATP)). In mice exposed to 98% PO(2) for 36 hr, ΔI(sc,forsk) decreased, ΔI(sc,amil) and ΔI(sc,ATP) was not affected. In gulo(-/-) mice, both ΔI(sc,forsk) and ΔI(sc,ATP) decreased from three weeks after Vit-C deprivation, while both were unchanged with Vit-C supplementation. At the fourth week, tissue resistance and all electrolyte transport activities were decreased. An immunofluorescence study showed that the expression of cystic fibrosis conductance regulator (CFTR) was decreased in gulo(-/-) mice, whereas the expression of KCNQ1 K(+) channel was preserved. Taken together, the CFTR-mediated Cl(-) secretion of airway epithelium is susceptible to oxidative stress, which suggests that supplementation of the antioxidant might be beneficial for the maintenance of airway surface liquid.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Yeryung
authors.initials: Y
authors.lastname: Kim
authors.forename: Hyemin
authors.initials: H
authors.lastname: Kim
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Yoo
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Kang
authors.forename: Sung Joon
authors.initials: SJ
authors.lastname: Kim
authors.forename: Jin Kyoung
authors.initials: JK
authors.lastname: Kim
authors.forename: Hyun Sung
authors.initials: HS
authors.lastname: Cho
mesh_terms: D000818:Animals; D001206:Ascorbic Acid Deficiency / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D006931:Hyperbaric Oxygenation; D018496:Hyperoxia / Q000503:physiopathology*; D017136:Ion Transport / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout / Q000378:metabolism; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D018384:Oxidative Stress; D010100:Oxygen / Q000009:adverse effects / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium; D013400:Sugar Acids / Q000378:metabolism
chemical_list: D002712:Chlorides; D015221:Potassium Channels; D013400:Sugar Acids; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; C007895:gulonolactone; D012964:Sodium; D010100:Oxygen